**2. Modern antibiotic era**

Modern antibiotic era began in 1904–1910 with Paul Ehrlich and Alexander Fleming [4, 5]. Initially, it was limited to the discovery of chemicals like inorganic mercury salts and organoarsenic compounds to treat syphilis. It was Paul Ehrlich who introduced the systemic screening approach that is the cornerstone of modern drug research trials [4]. Paul Ehrlich and his team synthesised hundreds of organo-arsenic derivatives of a very toxic drug Atoxyl and tested them in rabbits infected with syphilis. This approach led to the discovery of Salvarsan and later to a sulfa drug (Prontosil). The serendipitous discovery of penicillin by Alexander Fleming in 1928 changed the history of infectious diseases [5]. It was Florey and Chain who led the pathway for purification of penicillin and later to its mass production [6]. Interestingly enough, Fleming was the one who sounded the warning bells regarding the development of resistance to the penicillin, if not used properly. So, in a nutshell, discovery of the first three antimicrobials, Salvarsan, Prontosil and penicillin paved the pathway for the discovery of newer antibiotics in future.

The golden era of discovery of newer antibiotics continued and lasted till 1970s when most of the major classes like tetracyclines, methicillin, gentamicin, etc. were discovered [7]. This was followed by apparent absence of newer drug discovery with occasional antibiotic making an appearance here and there. Simultaneously, we made each newly discovered antibiotic ineffective after its launch by extensive use and misuse for trivial illnesses. The prime example of this is the fluoroquinolone, ciprofloxacin [8]. It was one of the most active, broad-spectrum antibiotics which had minimum side effects and a very good bioavailability upon oral use and soon became a drug of choice for many infections. Its extensive usage for gastroenteritis and respiratory infections, which were mostly viral in origin, led to the development of high level of resistance especially in developing countries.

action of β-lactamases) and (iii) pumped out from the cell as in efflux pump mechanisms

Introductory Chapter: Stepping into the Post-Antibiotic Era—Challenges and Solutions

http://dx.doi.org/10.5772/intechopen.84486

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**Figure 1.** Timeline showing antibiotic development and antimicrobial resistance.

Unfortunately, true burden of antimicrobial resistance (AMR) remains unknown. There are many hindrances in estimating the burden of AMR. Incongruent data is available from public and private sectors; data are often not collected properly and contain little information of patient follow up. These problems are intensified in low- and middle-socioeconomic countries due to problems of inadequate surveillance, poor laboratory infrastructure and limited access to the crucial antimicrobials. According to a study from Vietnam and Thailand, prevalence of stool carriage of extended-spectrum beta-lactamase (ESBL)-producing *Escherichia coli* was 51.0 and 69.3%, respectively [13]. There is also an increasing prevalence of MDR Grampositive bacteria. Another study in Thailand and Indonesia showed that prevalence of MRSA carriage is around 8% in admitted patients [14, 15]. Similar or worse situation exists in other Asian countries including China, Pakistan, Bangladesh and India. Antimicrobial resistance is a global issue. Resistance genes spread throughout the world as recent database lists the existence of more than 20,000 potential resistance genes (r genes) of nearly 400 different types, predicted from available sequences [16]. It is difficult to estimate the exact AMR burden due to the lack of comprehensive and uniform data. Gram-negative bacteria possessing the capabilities of producing extended-spectrum beta-lactamases (ESBL), AmpC beta-lactamases and carbapenemases have emerged as a therapeutic challenge for medical fraternity [17]. *Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa*, and *Enterobacter* species have been classified into a group known as "ESKAPE" due to their ability to escape the action of antimicrobials [18]. Multiple mechanisms of antimicrobial resistance have been acquired by carbapenem-resistant *Enterobacteriaceae* (CRE), *P. aeruginosa* and *A. Baumannii* resulting in enhanced morbidity and mortality [19–23]. In the 1990s,

of resistance [12].
